GNAS mutation

Assessment by the intact FGF23: total FGF23 ratio as well as gallium-DOTATATE scan suggested that the vertebral body lesion could represent FD. Other than understanding difference in underlying molecular processing of FGF23 in PMT and FD, testing for mutations, imaging studies as well as in situ hybridization helped solve the questions arising from this unique case of coexistence of PMT and FD.

NGS analysis of pancreatic cyst fluid demonstrates high specificity and may serve as an additional diagnostic tool to CEA. Combining cystic fluid CEA and NGS increases the accuracy in determining whether a lesion is mucinous and NGS showed a higher diagnostic accuracy in advanced lesions compared to CEA. While the absence of alarming NGS findings should not preclude surgical treatment, patients with alarming mutations should be considered for surgery.

GNAS mutations are prevalent among Chinese acromegaly patients, correlating with reduced pituitary tumor sizes and enhanced GH secretion functions. Our findings underscore the influence of gender on the clinical manifestations of GNAS mutations. Accordingly, we recommend that future clinical and foundational researches on acromegaly give heightened consideration to gender-specific differences.

No abstract available

Survival outcome was more closely associated with the grade of the peritoneal disease than with the grade of the primary neoplasm. Our findings support the developing concept that mutational analysis may provide prognostic information in patients with PMP.

CDK4/6 inhibition with palbociclib had clinical activity in PMC characterized by mutations in GNAS that was superior to that previously reported with cytotoxic chemotherapy. CDK4/6 inhibition is a novel therapeutic strategy worthy of further evaluation in this subgroup of gastrointestinal neoplasms.

This first reported case of primary jugular foramen fibrous dysplasia highlights the importance of considering this diagnosis when evaluating jugular fossa lesions. Understanding the anatomy of the infratemporal and jugular fossae, along with proficiency in microsurgical techniques, is essential for removing such tumors while preserving cranial nerve functions and the patient's quality of life. https://thejns.org/doi/10.3171/CASE24396.

Our findings indicate two key points: First, mutations within the MAPK pathway, particularly in KRAS, are evident across all tumors, along with a high frequency of GNAS mutations. Second, progression toward PMP or adenocarcinoma is associated with an accumulation of additional mutations within common oncogenic pathways.

Our study highlights the importance of accurate diagnosis established on multifaceted assessment for the effective treatment of ERMS. We present compelling evidence supporting the clinical use of anlotinib as a promising treatment strategy for pediatric ERMS patients, especially for those resistant to conventional chemotherapy.

Paediatric PA present multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor Interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

Study observed mutations in GNAS gene in blood samples from FD cases. However, a limitation is that only DNA extracted from blood underwent successful exome sequencing. Potential reason for low-quality DNA extraction from tissue may be attributed to prior fixation procedures conducted on bone specimens.

GNAS is highly expressed in osteosarcoma and associated with poor prognosis, acting as an oncogene in osteosarcoma progression. Targeting GNAS could be a potential therapeutic strategy for osteosarcoma. Further studies on GNAS-related signaling pathways may provide deeper insights into the molecular mechanisms driving osteosarcoma malignancy.

Multiple orthogonal approaches demonstrate that Kras G12D and Gnas R201C co-expression results in a gene signature of gastric pyloric metaplasia and glycolytic dependency during IPMN pathogenesis. The observed metabolic reprogramming may provide a potential target for therapeutics and interception of IPMNs.

For selected IPMNs with non-intestinal, non-invasive, and branch duct, genetic assessment might be a helpful tool for predicting the possible development of concomitant PDAC, although a prospective validation study using a larger study population is needed.

In this pilot study, circulating tumor DNA was not detected in blood when the tumor harbored mutations of known significance. In the future, a study with a larger sample size is needed to confirm these findings and to determine whether ctDNA could identify patients at risk for early recurrence and/or systemic metastases.

Specific somatic mutations in GNAS, PTTG1, GIPR, HGMA2, MAST and somatic variants associated with cAMP, calcium signaling, and ATP pathways have also been associated with the development of acromegaly. This review focuses on the oncogenic mechanisms by which sporadic acromegaly can develop, covering a complex series of molecular alterations that ultimately alter the balance between proliferation and apoptosis, and dysregulated hormonal secretion.

We postulate that CPAs arise from a precursor lesion, SPNs, where two distinct cell populations might contribute differently to adrenocortical tumorigenesis. Our data also provide clues to the molecular mechanisms underlying the layered structures of human adrenocortical tissues.

In summary, NGS of BC samples increased the sensitivity of detecting biliary neoplasia compared with traditional cytology. Performing NGS on BC samples may help diagnose HGD or early CCA, benefiting the timing of liver transplantation.

We identified a relatively high frequency of PRKAR1A mutations in sporadic CM. These PRKAR1A mutations may also represent an important oncogenic mechanism in sporadic myxomas, as already known in CM cases associated with CNC.

However this study shows the increase in sensitivity in detection of cysts with IPMN/MCN pathology by combining size CEA and DNA analysis. These findings can validate serial surveillance by EUS with FNA as DNA and CEA levels can morph over time and also provide improved guidance on potential premalignant mucinous cysts.

In this retrospective study of serum tumor markers in patients with appendiceal adenocarcinoma, CEA, CA19-9, and CA125 were associated with overall survival in appendiceal adenocarcinoma. Given their value, all 3 biomarkers should be included in the initial workup of patients with a diagnosis of appendiceal adenocarcinoma.

The diagnosis of fibro-osseous lesions by hematoxylin and eosin alone is confusing and thus should be supported by relatively simple histomorphometric analysis for better treatment outcomes. At the diagnostic stage of fibro-osseous lesions, evaluation of intralesional vessel size, reliable molecular marker, and histochemical nature can aid in differentiating fibrous dysplasia from central ossifying fibroma and cemento-osseous dysplasia alongside, other clinical, radiographic and pathological criteria. These parameters help in the diagnostic decision-making of fibro-osseous lesions.

The recurrent alterations described in cysts provide an opportunity for diagnosis using aspirated cyst fluid. Molecular characterization of IPMNs shows a striking spatial and mutational heterogeneity, challenging traditional models of neoplastic development and creating challenges to interpretation of cyst fluid sequencing results.

The presence of a PRKACA/B fusion appears to contribute to oncocytic morphology, but 71% of fusion-positive cases had mixed epithelial subtypes. Rare cases harbored concurrent fusion and driver mutation associated with IPMN. Though fusion-positive lesions were more commonly seen in the non-recurrence group, they also comprised >50% of cases with disease recurrence.

BMPR1A G298D mutation was exclusively identified in a subset of driverless neoplasms which were classified as granulosa cell tumors (3/27=11%). For BMPR1A-mutant tumors, the overall absence of any detectable known driver mutations supports our hypothesis that this alteration could be an alternative rare tumorigenic mechanism.

In conclusion, our findings demonstrate that GNAS mutation results in the growth suppression of CRC cells. Moreover, the GNAS mutation-induced overexpression of PDE4D provides a potential avenue to impede the proliferation of CRC cells through the use of PDE4 inhibitors.

Cyst fluid CEA continues to be a useful test in the diagnosis of mucinous pancreatic cysts but does not appear as specific as previously reported. Raising the CEA threshold to 250 ng/mL to maintain specificity for differentiating mucinous from non-mucinous cysts may be considered.

Diagnosis and therapeutic management of benign craniofacial bone lesions remains challenging. If surgical treatment is contemplated, the morbidity of the intervention should always be weighed against the potential benefits. Evolution of extended endoscopic endonasal and transorbital surgery means that more lesions can be reached purely endoscopically with better oncological and cosmetic results.

Furthermore, the ICGC database demonstrated a 10.6 % mutation frequency for GNAS in HCC patients. The coordination of elevated anti-GNAS autoantibody, high expression of GNAS in the mRNA and protein levels in HCC, and high frequency of GNAS mutation indicates that anti-GNAS autoantibody may be used as an early indicator of HCC.

EUS-FNA, however, entails risks like infection and needle tract seeding, emphasizing the need for proper utilization. Pancreatic cyst fluid analysis augments diagnostic accuracy and informs clinical decisions, making it a valuable adjunct to imaging.

Surprisingly, the clonal mutations were not well mixed in the BM with regions of high clonal diversity millimeters away from regions with a paucity of these mutated clones. Future work will expand this platform to describe BM clonal architecture in a larger set of bone marrow specimens and a wide variety clinical scenarios to help further explain the role of the BM niche in CH, MPNs and leukemia.

Among the 67 AFTN evaluated in this study, 50% presented with normal serum TSH, 70% displayed ultrasound features suggesting an intermediate malignancy risk and 50% of the AFTN submitted to cytology yielded indeterminate results. No malignant AFTN was detected.

Three-hundred and ninety-four patients (32.2%) received hypomethylating agents (azaciticine, N=367; decitabine, N=27), and 158 patients (12.9%) underwent allogeneic haematopoietic stem cell transplantation... Combining genomic with hematological and cytogenetic parameters, the Asian clinical-molecular prognostic model improved the risk stratification of patients with MDS in Asia, potentially improving clinical decision-making.

Detecting GNAS mutations in liver tissue may shorten diagnostic time and is of particular interest in the partial and atypical forms of MAS with neonatal cholestasis. Neonatal cholestasis in children with MAS can self-resolve, but liver dysfunction and malignant lesions persist.

We analyzed PRKACA/B fusion genes including ATP1B1-PRKACA, DNAJB1-PRKACA, and ATP1B1-PRKACB by reverse transcription PCR (RT-PCR); mRNA expression of fusion genes and non-rearranged PRKACA/B genes by quantitative RT-PCR; mutations in KRAS, BRAF, and GNAS by targeted sequencing or droplet digital PCR; and the expression of cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and beta (PRKACB), phosphorylated-CREB, and aberrations of p16, p53, SMAD4, STK11, and β-catenin by immunohistochemistry...In conclusion, PRKACA/B fusion genes are not only the characteristic drivers of IOPNs, but also play a crucial role in the development of subclonal oncocytic neoplasms. Moreover, oncocytic morphology is strongly associated with upregulation of PRKACA/B, which may provide clues for potential therapeutic options.

IL-1b-mediated Regnase-1 downregulation induces MDSCs and promotes pancreatic cancer through the evasion of anticancer immunity.

Transient pregnancy-induced Cushing's syndrome may be associated with somatic GNAS mutations and altered adrenal pathology due to abnormal activation of LHCGR.

We achieved increasingly precise and biologically relevant biomarkers by using data-driven CD3/CD8 density cutoffs and ratios, while controlling for important clinicopathologic and molecular variables in CRC. Independent validation and inclusion of other immune or stromal cell types will bring these findings closer to clinical utility in CRC.

GAFG exhibits diversity at the molecular level, and GNAS mutations are more common than KRAS mutations, TP53 mutations, and microsatellite instability. To date, no association between EBV/HER2 and GAFG has been found.

P3, N=140, Recruiting, Fundacion Clinic per a la Recerca Biomédica | Not yet recruiting --> Recruiting | Initiation date: Jun 2023 --> Sep 2023

DNA methylation profiling confirmed the existence of three molecular subtypes of somatotroph PitNETs. High expression of NR5A1 and GIPR in subtype 1 tumors is correlated with specific methylation of both genes.